1. H.R.Sarreshtahdar, MD Occupational Medicine Specialist
Heavy Metal Toxicity
H.R.Sarreshtahdar, MD
Occupational Medicine Specialist
Arsenic
Lead
Mercury

2. HEAVY METALS
The term heavy metal refers to any metallic chemical element that has a relatively high density and is toxic or poisonous at low concentrations.

3. HEAVY METALS Are natural components of the Earth's crust
To a small extent they enter our bodies via food, drinking water and air
As trace elements, some heavy metals (e.g. copper,
selenium, zinc) are essential to maintain the metabolism
of the human body however, at higher concentrations
they can lead to poisoning
Heavy metal poisoning could result, for instance, from drinking-water contamination (e.g. lead pipes), high ambient air concentrations near emission sources, or intake via the food chain

4. Mercury - Hg
Mercury is the only common metal which is liquid at ordinary temperatures. It rarely occurs free in nature and is found mainly in cinnabar ore (HgS) in Spain and Italy. It alloys easily with many metals, such as gold, silver, and tin - these alloys are called amalgams. Its ease in amalgamating with gold is used in the recovery of gold from its ores.

5. Health effects of mercury
Disruption of the nervous system
Damage to brain functions
DNA damage and chromosomal damage
Allergic reactions, resulting in skin rashes,
Tiredness and headaches
Negative reproductive effects, such as sperm damage, birth defects and miscarriages

6. Environmental effects of mercury
Fish are organisms that absorb great amounts of methyl mercury from surface waters every day (mercury can accumulate in fish and in the food chains)
The effects that mercury has on animals are: kidneys damage, stomach disruption, damage to intestines, reproductive failure and DNA alteration

8. What is Cadmium?
A metal most often encountered in earth’s crust combined with chlorine (cadmium chloride), oxygen (cadmium oxide), or sulfur (cadmium sulfide)
Exists as small particles in air, result of smelting, soldering or other high temp. industrial processes
By-product of smelting of zinc, lead, copper ores
Used mainly in metal plating, producing
pigments, batteries, plastics and as a
neutron absorbent in nuclear reactors
Cadmium is used in batteries

9. Cadmium and Smelters/Mine Sites
Cadmium is a by-product of smelters
Has been a concern at the Summitville mine site in Colorado
Photo of Smelter

10. Exposure Sources - Tobacco
Tobacco smoke (a one pack a day smoker absorbs roughly 5 to 10 times the amount absorbed from the average daily diet)
Tobacco smoke is an important source of cadmium exposure

11. Exposure Sources – By Mouth
Foods (only a small amount is absorbed)
Itai Itai disease (cadmium contamination + diet low in calcium & vitamin D)

12. Cadmium – Cd HEALTH EFFECTS
Human uptake of cadmium takes place mainly through food
Foodstuffs that are rich in cadmium can greatly increase the cadmium concentration in human bodies (liver, mushrooms, shellfish, mussels, cocoa powder and dried seaweed)

13. Why Is Cadmium a Health Hazard?
Affects lungs & kidneys
2o effects on skeletal system
Binds to sulfhydryl groups, displacing other metals from metalloenzymes, disrupting those enzymes
Competes with calcium for binding sites on regulatory proteins

14. Respiratory Effects Acute inhalation may mimic metal fume fever
Fever, chills & decreases in FVC and FEV1
Initial symptoms: flu-like symptoms
Later: chest pain, cough, dyspnea
Bronchospasm and hemoptysis may occur
Chronic inhalation MAY result in impairment of pulmonary function with reduction in ventilatory capacity

15. Renal Effects
May cause tubular and glomerular damage with resultant proteinuria
May follow chronic inhalation or ingestion
Latency period of ~10 yrs
Nephropathy is progressive & irreversible

16. Renal Effects Chronic exposure – progressive renal tubular dysfunction
Toxic effects are dose related
Critical renal concentration
Decreased GFR
Chronic renal failure
Kidney stones more common

17. Skeletal Effects Bone lesions occur late in severe chronic poisoning
Pseudofractures
Other effects of osteomalacia and osteoporosis
Appear to be secondary to increased urinary calcium and phosphorus losses

18. Signs and Symptoms - Acute
Food poisoning (ingestion)
Bronchitis (inhalation)
Interstitial pneumonitis (inhalation)
Pulmonary edema (inhalation)
A condition that mimics metal fume fever
Children who eat dirt (pica behavior) are at risk

19. Signs & Symptoms - Chronic
Chronic exposure may result in renal dysfunction and bone disease
Mild anemia, anosmia & yellow discoloration of the teeth may occur
Chronic exposure may effect the sense of smell

20. HEALTH EFFECTS Diarrhoea, stomach pains and severe vomiting
Bone fracture
Reproductive failure and possibly even infertility
Damage to the central nervous system
Damage to the immune system
Psychological disorders
Possibly DNA damage or cancer development

21. Chromium - Cr
Chromium(III) is an essential nutrient for humans and shortages may cause heart conditions, disruptions of metabolisms and diabetes
But the uptake of too much chromium(III) can cause health effects as well, for instance skin rashes

22. Chromium - Cr
Chromium(VI) is a danger to human health, mainly for people who work in the steel and textile industry People who smoke tobacco also have a higher chance of exposure to chromium Hexavalent Chromium – Chromium (VI) is a species of chromium that is forbidden to use in electrical & electronic industry.

23. HEALTH EFFECTS
When it is a compound in leather products, it can cause allergic reactions, such as skin rash
After breathing it in, chromium(VI) can cause nose irritations and nosebleeds
Upset stomachs and ulcers
Respiratory problems
Weakened immune system
Kidney and liver damage
Alteration of genetic material
Lung cancer
Death

24. Environmental effects of chromium
Chromium(III) is an essential element for organisms that can disrupt the sugar metabolism and cause heart conditions, when the daily dose is too low
Chromium(VI) is mainly toxic to organisms - it can alter genetic materials and cause cancer

25. Lead - Pb
Foods such as fruit, vegetables, meats, grains, seafood, soft drinks and wine may contain significant amounts of lead
Cigarette smoke also contains small amounts of lead

26. Lead sources application of lead in gasoline fuel combustion
industrial processes
solid waste combustion

27. Lead Paint The use of lead in residential paint was banned in 1977
Lead-containing pigments still are used for outdoor paint products because of their bright colors and weather resistant properties
Tetraethyl and tetramethyl lead are still used as additives in gasoline in several countries

28. ToxicoKinetics and ToxicoDynamics
Absorption:
Lungs: depends on size particle
GI:
Adults: 20-30%
Children: as much as 50% of dietary lead
Inadequate intake of iron, calcium, and total calories are associated with higher lead levels
Skin:
Inorganic lead is not absorbed
Organic lead is well absorbed
Lead is carried bound to the RBC

29. PharmacoKinetics and PharmacoDynamics
Distributed extensively throughout tissues: bone, teeth, liver, lung, kidney, brain, and spleen
Body lead storage: bones- can constitute a source of remobilization and continued toxicity after the exposure has ceased
Lead crosses the BBB and concentrates in the gray matter
Lead crosses the placenta
Excretion:
Kidneys. The excretion increases with increasing body stores (30g-200 g/day)
Feces

30. Signs and Symptoms of Lead Toxicity
Fatigue
Irritability
Lethargy
Paresthesis
Myalgias
Abdominal pain
Tremor
Headache
Vomiting
Weight loss
Constipation
Loss of libido
Motor neuropathy
Encephalopathy
Cerebral edema
Seizures
Coma
Severe abdominal cramping
Epiphyseal lead lines in children (growth arrest)
Renal failure

31. Range of Lead-induced Health Effects in Adults and Children
Blood lead levels
Adults
Children
10 g/dL
Hypertension may occur
Crosses placenta
Impairment IQ, growth
Partial inhibition of heme synthesis
20 g/dL
Inhibition of heme synthesis
Increased erythrocyte protoporphyrin
Beginning impairment of nerve conduction velocity
30 g/dL
Systolic hypertension
Impaired hearing()
Impaired vitamin D metabolism
40 g/dL
Infertility in males
Renal effects
Neuropathy
Fatigue, headache, abd pain
Hemoglobin synthesis inhibition
50 g/dL
Anemia, GI sx, headache, tremor
Colicky abd pain, neuropathy
100 g/dL
Lethargy, seizures, encephalopathy
Encephalopathy, anemia, nephropathy, seizures

32. Health effects of lead
Disruption of the biosynthesis of haemoglobin and anemia
A rise in blood pressure
Kidney damage
Miscarriages
Disruption of nervous systems
Brain damage
Declined fertility of men through sperm damage
Diminished learning abilities of children
Behavioural disruptions of children, such as aggression, impulsive behaviour and hyperactivity

33. Health effects of lead
Lead can enter a foetus through the placenta of the mother
Because of this it can cause serious damage to the nervous system and the brains of unborn children
That is why women in pregnancy can not work with lead.

34. The average lead level of American children is 2 g/dl
8.9% of American children have lead poisoning
Lead intoxication is more prevalent in minority groups and among those living in the northeast

35. Diagnosis Evaluation of clinical symptoms and signs CBC
Serum iron levels, TIBC, ferritin
Abdominal radiographs (for recent ingestion of lead-containing material)
Whole blood lead level
X-ray fluorescence (XRF)- to asses body burden

36. Arsenic

37. Introduction Commercial products Wood preservatives Pesticides
Herbicides
Fungicides
Food
Seafood and fish
Others
Antiparasitic drugs

38. Toxicokinetics
T1/2 of inorganic arsenic in the blood is 10 hrs and of organic arsenic is around 30 hours
2-4 weeks after the exposure ceases, most of the remaining arsenic in the body is found in keratin-rich tissues (nails, hair, skin)

39. Toxicokinetics
Inorganic arsenic is converted to organic arsenic (biomethylation to monomethyl arsonic- MMA or DMA) in the liver. This may represent a process of detoxification
Renally excreted (30-50% of inorganic arsenic is excreted in about 3 days). Both forms are excreted depend on the acuteness of the exposure and dose

40. Manifestations of acute arsenic poisoning
Bodily system affected
Symptoms or signs
Time of onset
Systemic
Thirst
Hypovolemia, Hypotension
Minutes
Minutes to hours
Gastrointestinal
Garlic or metallic taste
Burning mucosa
Nausea and vomiting
Diarrhea
Abdominal pain
Hematemesis
Hematochezia, melena
Rice-water stools
Immediate
Hours
Hematopoietic system
Hemolysis
Hematuria
Lymphopenia
Pancytopenia
Several weeks
Pulmonary
(primarily in inhalational exposures)
Cough
Dyspnea
Chest Pain
Pulmonary edema
Liver
Jaundice
Fatty degeneration
Central necrosis
Days
Kidneys
Proteinuria
Acute renal failure
Hours to days

41. PALMAR KERATOSIS

42. Biological Monitoring
Urinary arsenic measurement
Spot sample (mcg/L)
Timed urine collection (mcg/24 hours)
Normal values
Spot urine= ~10 mcg/L ( mcg/L)
24 hours urine collection=<25 mcg/24 hours
Whole blood= <1mcg/L (usually is elevated in acute intoxication)

43. Chromium
Common oxidation states Cr+3 & Cr+6, in aerobic conditions Cr exists primarily as the chromate ion –highly soluble, toxic, can dimerize to dichromate
Anerobic (reducing) conditions Cr exists the +3 ion; not very toxic or soluble under basic neutral or even acidic conditions
Env. Chemistry, Baird & Cann

44. Cr Contamination of Water
Used for electroplating, corrosion resistance & tanning
Second most abundant inorganic contaminant of groundwater under hazardous waste sites
MCL in US 100 ppb
Removal –most heavy metals increase the pH but Cr+6 soluble at any pH but Cr+3 low solubility so Cr+6 usually reduced to +3
Env. Chemistry, Baird & Cann